Background/Purpose

The systemic depletion of B cells induced by mabthera, a monoclonal antibody against human CD20, has shown to be an effective therapy for controlling disease activity in rheumatoid arthritis (RA), but not in psoriatic arthritis (PsA) patients. This strongly suggests that B cells play a different role of in the pathogenesis of these diseases. It has been suggested that B cells participate in the pathogenesis of chronic synovitis through several mechanisms, including T-cell activation by acting as antigen-presenting cells. Objective: To study the potential differences in antigen-presenting phenotypes of B cells present in the synovial microenvironment of RA and PsA patients. 

Methods

The surface expression levels of CD27, CD23, class II molecules (HLA-DP, -DQ and -DR), CD40 and CD86 were assessed by double- or triple-staining flow cytometry on CD20+ cells from peripheral blood (PB) and synovial fluid (SF) of 13 RA and 15 PsA patients. Flow cytometry analysis data are presented as relative mean fluorescence intensity with respect to cells in PB, which was considered 100%. The expression of interferon-induced protein IFIT-4, which is involved in the differentiation of monocytes into dendritic cells, was assessed by quantitative RT-PCR in negatively immunoselected CD19+ B cells from SF and PB of RA patients.

Results

Analyzing all patients included in this study, the percentage of mononuclear CD20+ cells in SF (2.24±0.37%) was significantly lower than in PB (8.59±1.26%, p<0.01). When these data were compared in RA versus PsA patients, the percentages of CD20+ cells in PB and SF were similar in both range and tendency. B cells from SF of RA and PsA patients showed an activated phenotype (down-regulation of CD23) and seem to have had in contact with the antigen (up-regulation of CD27). Flow cytometry analyses showed an increased expression of HLA-DR and -DQ in CD20+ cells from SF compared to those from PB, in both RA (277.84±65.66; 262.20±108.81) and PsA (267.86±88.53; 311.08±116,65) patients. HLA-DP was also elevated in rheumatoid SF B cells (1009.48±335.70), although conversely, a significantly lower expression of this class II molecule was observed in SF from PsA patients (46.38±19.73). Surface expression of CD86 was higher in SF than in PB B cells from both pathologies (RA: 629.79±172.24; PsA: 326.46±138.77). CD40 expression was significantly lower in SF compared to PB in B cells from RA patients (66.31±12.21); however, this was not the case in PsA patients (243.76±71.18). Interestingly, CD20 surface expression was 35% lower in B cells (CD19+, CD138-) from SF with respect to PB in RA patients. Finally, qRT-PCR showed approximately a 5-fold increase in IFIT-4 mRNA content in B cells from SF compared to PB in RA patients. 

Conclusion

These data show that B cells in the synovial microenvironment of RA and PsA patients show a differential phenotype respect to molecules involved in antigen presentation and co-stimulation, which suggest that B cells play a different role in the pathogenesis of these two pathologies. This could have implications for the understanding of the dissimilar clinical response to B cell-depleting treatment observed in RA and PsA.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/differential-antigen-presenting-b-cell-phenotype-from-synovial-microenvironment-of-rheumatoid-arthritis-and-psoriatic-arthritis-patients/